We propose a CERTs Research Center (RC) with the theme of improving outcomes for children by optimizing the use of therapeutics. Additional sub-themes, with expected impact beyond pediatrics, are pharmacogenomics and personalized medicine, patient safety, and quality improvement methodology. The RC will link Cincinnati Children's Hospital Medical Center (an acknowledged leader in innovation and improvement), a research core skilled in evaluation science, improvement science, and education (led by the Center for Health Care Quality at CCHMC);and partners capable of disseminating research and education programs to the vast majority of the nation's pediatric practitioners and tertiary care settings (the American Board of Pediatrics (ABP;a certifying body), the National Association of Children's Hospitals and Related Institutions (NACHRI), Children's Hospital Corporation of America (CHCA), Ohio Medicaid, the University of Cincinnati School of Pharmacy, UnitedHealth Group, and several parent organizations). Within this framework, our specific aims are to: 1) Create a research core that brings together individuals with broad expertise in evaluation, health services research, quality improvement methods, analysis of large databases, quality of life, chronic illness, and medication adherence and, 2) Develop and implement a range of educational approaches that will result in broad improvements in the use of therapeutics in the pediatric population. These specific aims will be accomplished, in part, through four pilot projects at different stages of innovation and dissemination that will: 1) test the impact of pharmacogenetic testing on the treatment of children on risperidone;2) decrease harm from adverse drug events using high reliability methods;3) improve outcomes for children with chronic illness through collaborative networks in subspecialty care by working initially with the Pediatric Inflammatory Bowel Disease Network (PIBDNet) to improve medication management, and 4) pilot and disseminate resources that facilitate the use of optimal therapeutics by working with the American Academy of Pediatrics (AAP). Although these projects all focus on care for children, the methods and knowledge generated will go far beyond the pediatric population and will advance the field of therapeutics by creating new knowledge about how to integrate pharmacogenetic information effectively into clinical practice, high reliability methods into care systems, and how to use quality improvement methods and collaborative learning to test and accelerate the diffusion of innovations into practice.